Two-tiered universal newborn screening strategy for severe combined immunodeficiency

Abstract

Outcomes for infants with severe combined immunodeficiency (SCID) would be improved by universal newborn screening, but there are not yet screening tests of sufficient accuracy for the disorder. In a pilot study, we assessed the ability of a two-tiered strategy to improve accuracy. Dried blood samples from patients were assessed with two tests for lymphopenia: interleukin-7, a T-cell growth cytokine, and TRECs, a byproduct of T-cell receptor recombination. IL-7 screening has a specificity of 96.1% and TRECs have a specificity of 92.3%. Combining these tests in a two-tiered strategy increases specificity to 100% (97–100% CI). Sensitivity was 85% for IL-7 screening and 100% for TREC screening. A two-tiered strategy may be of sufficient accuracy to enable universal SCID screening, and should be assessed in a prospective trial.